KLF1 Promotes Non-Small Cell Lung Cancer Cell Proliferation and Invasion by Upregulating the LINC02159/DYNC1H1 Pathway.

Abstract

Non-small cell lung cancer (NSCLC) is a common and fatal malignancy. This study aimed to elucidate the mechanism of Kruppel-like factor (KLF1) in NSCLC progression. Clinical samples were collected, after which the expression levels of KLF1, LINC02159, and dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in tissues and cells were initially detected, and NSCLC cell proliferation and invasion were measured when KLF1 was up- or downregulated. The binding relationships among KLF1, the LINC02159 promoter, DYNC1H1, and serine and arginine-rich splicing factor 1 (SRSF1) were analyzed. The colocalization of LINC02159 and SRSF1 was verified. DYNC1H1 stability upon actinomycin D treatment was assessed. Combined experiments were designed to confirm the interaction of the LINC02159/DYNC1H1 pathway in NSCLC development. Finally, xenograft tumors were generated in nude mice to validate the mechanism involved. KLF1, LINC02159, and DYNC1H1 were upregulated in NSCLC tissues and cells. KLF1 overexpression promoted NSCLC cell proliferation and invasion, whereas KLF1 knockdown inhibited NSCLC cell proliferation and invasion. Mechanistically, KLF1 transcriptionally activated LINC02159, which could recruit the SRSF1 protein and increase DYNC1H1 mRNA stability in the cytoplasm. Combined experiments revealed that LINC02159 and DYNC1H1 overexpression could counteract the inhibitory effect of KLF1 silencing on NSCLC cell proliferation and invasion. KLF1 silencing inhibited tumor growth in vivo by downregulating the LINC02159\DYNC1H1 pathway.